Cover.ƒ 10/27/03 11:37 AM Page 1
Understanding the

Immune System


How It Works


U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

NATIONAL INSTITUTES OF HEALTH 

National Institute of Allergy and Infectious Diseases 

National Cancer Institute 

NIH Publication No. 03-5423 

September 2003 

www.niaid.nih.gov 

www.nci.nih.gov 
1 Introduction 

2 Self and Nonself 

3 The Structure of the Immune System 

7 Immune Cells and Their Products 

19 Mounting an Immune Response 

24 Immunity: Natural and Acquired 

28 Disorders of the Immune System 

34 Immunology and Transplants 

36 Immunity and Cancer 

39 The Immune System and the Nervous Sy

40 Frontiers in Immunology 

45 Summary 

47 Glossary 
The immune system is a network 

cells, tissues*, and organs that w

together to defend the body agains

by “foreign” invaders. These are pr

microbes (germs)—tiny, infection-c

organisms such as bacteria, viruses

parasites, and fungi. Because the h

body provides an ideal environmen

many microbes, they try to break i

the immune system’s job to keep th

or, failing that, to seek out and destr

When the immune system hits the 

target or is crippled, however, it ca

unleash a torrent of diseases, inclu

allergy, arthritis, or AIDS.

The immune system is amazingly c

It can recognize and remember mil

different enemies, and it can produ

secretions and cells to match up w

wipe out each one of them.

The secret to its success is an elab

and dynamic communications netw

Millions and millions of cells, orga

into sets and subsets, gather like c

bees swarming around a hive and 

information back and forth. Once i

Bacteria:

streptococci

Fungus: 

penicillium mold

Parasite:

schistosome

Virus: 

herpes virus

*Definitions of words printed in italics are li

Glossary on page 47.
powerful chemicals. These substan

allow the cells to regulate their own 

growth and behavior, enlist their fe

and direct new recruits to trouble s

Self and Nonself 

he key to a healthy immune syst

its remarkable ability to distingu

between the body’s own cells—self

foreign cells—nonself. The body’s i

defenses normally coexist peacefull

cells that carry distinctive “self” ma

molecules. But when immune defen

encounter cells or organisms carryi

T

2 

Antigen Marker molecule A

Antigens carry marker molecules that identify 

as foreign. 
Anything that can trigger this imm

response is called an antigen. An a

can be a microbe such as a virus, o

a part of a microbe. Tissues or cell

another person (except an identical 

also carry nonself markers and act 

antigens. This explains why tissue 

transplants may be rejected. 

In abnormal situations, the immun

can mistake self for nonself and lau

attack against the body’s own cells 

tissues. The result is called an auto

disease. Some forms of arthritis and 

diabetes are autoimmune diseases. 

cases, the immune system respond

seemingly harmless foreign substan

as ragweed pollen. The result is all

and this kind of antigen is called an 

The Structure of the Immune System 

he organs of the immune system 

positioned throughout the body. 

are called lymphoid organs because 

are home to lymphocytes, small wh

blood cells that are the key players i

immune system. 

T
Tonsils and 

adenoids 

Lymph 

nodes 

Lym

nod

Lym

ves

Appendix 

Bone 

marrow 

Thy

Spl

Pey

patc

Lym

nod

Lym

ves

The organs of the immune system are position

throughout the body. 

Bone marrow, the soft tissue in the 

center of bones, is the ultimate sou

all blood cells, including white bloo

destined to become immune cells. 

The thymus is an organ that lies be

the breastbone; lymphocytes known 

4

Germinal 

center 

Follicle 

Medulla 

Vein 

Artery 

Outgoing 

lymph vesse

Pa

The lymph node contains numerous specialize

structures. T cells concentrate in the paracorte

B cells in and around the germinal centers, an

cells in the medulla. 

T lymphocytes, or just “T cells,” ma

the thymus. 

Lymphocytes can travel throughout 

body using the blood vessels. The c

also travel through a system of lym

vessels that closely parallels the bod

veins and arteries. Cells and fluids 

exchanged between blood and lymp

vessels, enabling the lymphatic sys

monitor the body for invading micr

The lymphatic vessels carry lymph, 

fluid that bathes the body’s tissues
in the neck, armpits, abdomen, and 

Each lymph node contains specializ

compartments where immune cells 

congregate, and where they can 

encounter antigens. 

Immune cells and foreign particles 

the lymph nodes via incoming lymp

vessels or the lymph nodes’ tiny bl

vessels. All lymphocytes exit lymph 

through outgoing lymphatic vessels

in the bloodstream, they are transp

tissues throughout the body. They p

everywhere for foreign antigens, th

gradually drift back into the lymph

system, to begin the cycle all over a

The spleen is a flattened organ at th

left of the abdomen. Like the lymph 

the spleen contains specialized 

compartments where immune cells 

and work, and serves as a meeting 

where immune defenses confront a

Clumps of lymphoid tissue are foun

many parts of the body, especially i

linings of the digestive tract and the 

airways and lungs—territories that 

gateways to the body. These tissues 

the tonsils, adenoids, and appendix

6

Lymph 

node 

Lymphatic 

vessel 

Immune cells and foreign particles enter th

nodes via incoming lymphatic vessels or th

nodes’ tiny blood vessels. 

Immune Cells and Their Products 

he immune system stockpiles a h

arsenal of cells, not only lympho

but also cell-devouring phagocytes a

their relatives. Some immune cells 

all comers, while others are trained 

highly specific targets. To work effe

most immune cells need the cooper

their comrades. Sometimes immune 

communicate by direct physical con

sometimes by releasing chemical mes

T

The immune system stores just a fe

each kind of the different cells need

recognize millions of possible enem

When an antigen appears, those few 

matching cells multiply into a full-s

army. After their job is done, they f
Heavy 

chain 

Light 

chain 

Variable region 

Constant region 

An antibody is made 

up of two heavy 

chains and two light 

chains. The variable 

region, which differs 

from one antibody to 

the next, allows an 

antibody to 

recognize its 

matching antigen. 

All immune cells begin as immatur

cells in the bone marrow. They resp

different cytokines and other signal

grow into specific immune cell type

as T cells, B cells, or phagocytes. Be

stem cells have not yet committed t

particular future, they are an intere

possibility for treating some immun

system disorders. Researchers curre

investigating if a person’s own stem 

can be used to regenerate damaged 

immune responses in autoimmune 

and immune deficiency diseases. 

B Lymphocytes 

B cells and T cells are the main typ

of lymphocytes. 

B cells work chiefly by secreting 

substances called antibodies into th

body’s fluids. Antibodies ambush a

circulating the bloodstream. They a

powerless, however, to penetrate ce

job of attacking target cells—either 

that have been infected by viruses 

that have been distorted by cancer—

to T cells or other immune cells 

(described below). 

8

Plasma cell Antibo

B cells mature into plasma cells that produce a

Each B cell is programmed to make 

specific antibody. For example, one 

will make an antibody that blocks a 

that causes the common cold, whil

another produces an antibody that 

a bacterium that causes pneumonia. 

When a B cell encounters its trigge

antigen, it gives rise to many large 

known as plasma cells. Every plasm

is essentially a factory for producin

antibody. Each of the plasma cells 

descended from a given B cell 

manufactures millions of identical 

antibody molecules and pours them 

the bloodstream. 
Immunoglobulins 

others fit more like a skeleton key. 

whenever antigen and antibody int

the antibody marks the antigen 

for destruction. 

Antibodies belong to a family of lar

molecules known as immunoglobul

Different types play different roles i

immune defense strategy. 

• Immunoglobulin G, or IgG, works 

efficiently to coat microbes, speed

their uptake by other cells in the 

immune system. 

• IgM is very effective at killing bac

• IgA concentrates in body fluids—t

saliva, the secretions of the respir

tract and the digestive tract—guar

entrances to the body. 

• IgE, whose natural job probably i

protect against parasitic infections

villain responsible for the sympto

of allergy. 

• IgD remains attached to B cells an

plays a key role in initiating early 

B-cell response. 

10

free-floating antigens. Rather, their 

contain specialized antibody-like re

that see fragments of antigens on th

surfaces of infected or cancerous ce

T cells contribute to immune defen

two major ways: some direct and re

immune responses; others directly a

infected or cancerous cells. 

Helper T cells, or Th cells, coordina

immune responses by communicati

other cells. Some stimulate nearby 

to produce antibody, others call in m

gobbling cells called phagocytes, still 

activate other T cells. 

Killer T cells—also called cytotoxic 

lymphocytes or CTLs—perform a di

function. These cells directly attack 

Mature helper 

T cell 

Mature cytoto

T cell 

Immature T cell 

Some T cells are helper cells, others are killer c
Surface contact 

Target-oriented 

granules 

Killer cell makes contact with target cell, trains 

weapons on the target, then strikes. 

cells carrying certain foreign or abn

molecules on their surfaces. CTLs a

especially useful for attacking virus

because viruses often hide from oth

of the immune system while they g

inside infected cells. CTLs recogniz

fragments of these viruses peeking 

from the cell membrane and launch 

attack to kill the cell. 

In most cases, T cells only recogniz

antigen if it is carried on the surfac

cell by one of the body’s own MHC

major histocompatibility complex, 

molecules. MHC molecules are prot

12

molecule provides a recognizable 

scaffolding to present a foreign anti

the T cell. 

Although MHC molecules are requi

T-cell responses against foreign inv

they also pose a difficulty during o

transplantations. Virtually every ce

body is covered with MHC proteins

each person has a different set of th

proteins on his or her cells. If a T c

recognizes a nonself MHC molecule 

another cell, it will destroy the cell

Therefore, doctors must match orga

recipients with donors who have th

closest MHC makeup. Otherwise th

recipient’s T cells will likely attack 

the transplanted organ, leading to 

graft rejection. 

Natural killer (NK) cells are anothe

of lethal white cell, or lymphocyte. 

killer T cells, NK cells are armed w

granules filled with potent chemica

But while killer T cells look for ant

fragments bound to self-MHC mole

NK cells recognize cells lacking self

molecules. Thus NK cells have the 

potential to attack many types of 

foreign cells. 
Macrophage 

Ma

Basophil 

Neutrophil 

Eosinophil 

Phagocytes, granulocytes, and mast cells, all w

different methods of attack, demonstrate the im

system’s versatility. 

Both kinds of killer cells slay on co

The deadly assassins bind to their t

aim their weapons, and then delive

lethal burst of chemicals. 

Phagocytes and Their Relatives 

Phagocytes are large white cells tha

swallow and digest microbes and o

foreign particles. Monocytes are 

phagocytes that circulate in the blo

When monocytes migrate into tissu

they develop into macrophages. 

Specialized types of macrophages c

found in many organs, including lu

kidneys, brain, and liver. 

14 
cells and other debris. They display 

of foreign antigen in a way that dra

attention of matching lymphocytes. 

they churn out an amazing variety 

powerful chemical signals, known 

as monokines, which are vital to th

immune responses. 

Granulocytes are another kind of im

cell. They contain granules filled w

potent chemicals, which allow the 

granulocytes to destroy microorgani

Some of these chemicals, such as 

histamine, also contribute to inflam

and allergy. 

One type of granulocyte, the neutro

also a phagocyte; it uses its prepack

chemicals to break down the micro

ingests. Eosinophils and basophils a

granulocytes that “degranulate,” sp

their chemicals onto harmful cells o

microbes nearby. 

The mast cell is a twin of the basop

except that it is not a blood cell. Ra

is found in the lungs, skin, tongue, 

linings of the nose and intestinal tr

where it is responsible for the symp

of allergy. 

A related structure, the blood platel

cell fragment. Platelets, too, contain 
activate some of the immune defen

Cytokines 

Components of the immune system 

communicate with one another by 

exchanging chemical messengers ca

cytokines. These proteins are secrete

cells and act on other cells to coordi

appropriate immune response. Cytok

include a diverse assortment of inter

interferons, and growth factors. 

Some cytokines are chemical switch

turn certain immune cell types on a

One cytokine, interleukin 2 (IL-2), t

the immune system to produce T ce

2’s immunity-boosting properties h

traditionally made it a promising tr

for several illnesses. Clinical studie

ongoing to test its benefits in other 

diseases such as cancer, hepatitis C

Cytokines include 

lymphokines, 

produced by 

lymphocytes, and 

monokines, made 

by monocytes and 

macrophages. 

Mature helper T cell Macrophage 

Lymphokines Mon

16

clinical benefit. 

Other cytokines chemically attract s

cell types. These so-called chemoki

released by cells at a site of injury 

infection and call other immune ce

the region to help repair the damag

fight off the invader. Chemokines o

play a key role in inflammation and 

a promising target for new drugs to 

regulate immune responses. 

Complement 

The complement system is made up 

about 25 proteins that work togethe

“complement” the action of antibod

destroying bacteria. Complement al

to rid the body of antibody-coated 

(antigen-antibody complexes). Com

proteins, which cause blood vessels 

become dilated and then leaky, con

to the redness, warmth, swelling, p

loss of function that characterize an 

inflammatory response. 

Complement proteins circulate in th

in an inactive form. When the first 

in the complement series is activate

typically by antibody that has locke

an antigen—it sets in motion a dom

effect. Each component takes its tu

precise chain of steps known as the 

complement cascade. The end produ
Antigen 

Antibody (IgG) 

First complement pro

Complement cascad

Cylindrical complex 

inserted in cell wall 

Cell 

swells 

and 

bursts 

The interlocking steps of the complement casc

cell death. 

cylinder inserted into—and punctur

hole in—the cell’s wall. With fluids 

molecules flowing in and out, the c

swells and bursts. Other componen

complement system make bacteria 

susceptible to phagocytosis or becko

cells to the area. 

18 
human disease. They range from t

common cold to debilitating condit

chronic hepatitis to life-threatening 

diseases such as AIDS. Disease-cau

microbes (pathogens) attempting to 

into the body must first move past 

body’s external armor, usually the s

cells lining the body’s internal passa

I

The skin provides an imposing barr

invading microbes. It is generally 

penetrable only through cuts or tiny 

abrasions. The digestive and respira

Comp

Macr

Lymphokines 

T cell 

Antibodies 

B cell 

Killer cell 

When challenged, the immune system has ma

weapons to choose. 
protection. Microbes entering the n

often cause the nasal surfaces to se

more protective mucus, and attemp

enter the nose or lungs can trigger 

sneeze or cough reflex to force mic

invaders out of the respiratory 

passageways. The stomach contains 

strong acid that destroys many path

that are swallowed with food. 

If microbes survive the body’s fron

defenses, they still have to find a w

through the walls of the digestive, 

respiratory, or urogenital passagewa

the underlying cells. These passage

are lined with tightly packed epithe

covered in a layer of mucus, effecti

blocking the transport of many orga

Mucosal surfaces also secrete a spe

class of antibody called IgA, which 

many cases is the first type of antib

encounter an invading microbe. 

Underneath the epithelial layer a nu

of cells, including macrophages, B 

and T cells, lie in wait for any germ 

might bypass the barriers at the sur

Next, invaders must escape a series 

general defenses, which are ready t

attack, without regard for specific a

markers. These include patrolling 

phagocytes, NK cells, and complem

20

just for them. Specific weapons, wh

include both antibodies and T cells

equipped with singular receptor str

that allow them to recognize and in

with their designated targets. 

Bacteria, Viruses, and Parasites 

The most common disease-causing 

microbes are bacteria, viruses, and 

parasites. Each uses a different tact

infect a person, and, therefore, each 

thwarted by a different part of the 

immune system. 

Most bacteria live in the spaces bet

cells and are readily attacked by 

antibodies. When antibodies attach 

bacterium, they send signals to 

complement proteins and phagocyt

to destroy the bound microbes. Som

bacteria are eaten directly by phago

which signal to certain T cells to jo

the attack. 

All viruses, plus a few types of bac

and parasites, must enter cells to su

requiring a different approach. Infe

cells use their MHC molecules to p

pieces of the invading microbes on 

cell’s surface, flagging down cytoto

T lymphocytes to destroy the infect

Antibodies also can assist in the im
Antibodies are triggered when a B cell 

encounters its matching antigen. 

The B cell takes in the antigen 

and digests it, 

Lymphokines secreted by 

the T cell allow the B cell to 

multiply and mature into 

antibody-producing plasma cells. 

Released into the bloodstream, antibodies lock onto 

matching antigens. These antigen-antibody complexes 

are soon eliminated, either by the complement cascad

or by the liver and the spleen. 

then it displays antigen fragme

bound to its own distinctive 

MHC molecules. 

The combination of antig

fragment and M

molecule a

the help of 

mature, ma

T cell. 

22

T cells are mobilized 

when they encounter a cell such as a macropha

or a B cell that has digested an antigen 

Some lymphokines 

attract immune cells— 

fresh macrophages, 

granulocytes, and 

other lymphocytes— 

to the site of infection. 

Yet other lymphokines 

direct the recruits once 

they arrive on the scene. 

and is displaying antigen fragmen

bound to its MHC molecules. 

Lymphokines 

help the T cell 

to mature 

The T cell, alert

and activated, 

secretes 

lymphokines. 

Some T cells 

become killer cells 

and track down 

body cells infected 

by viruses. 

Some 

lympho

spur th

growth 

more T 

Infected 

cells 
Parasites live either inside or outsid

Intracellular parasites such as the o

that causes malaria can trigger T-ce

responses. Extracellular parasites ar

much larger than bacteria or viruse

require a much broader immune at

Parasitic infections often trigger an 

inflammatory response when eosin

basophils, and other specialized gra

cells rush to the scene and release 

stores of toxic chemicals in an attem

destroy the invader. Antibodies also 

role in this attack, attracting the gra

cells to the site of infection. 

Immunity: Natural and Acquired 

Long ago, physicians realized that p

who had recovered from the plague 

never get it again—they had acquir

immunity. This is because some of 

activated T and B cells become mem

The next time an individual meets 

the same antigen, the immune syst

set to demolish it. 

Immunity can be strong or weak, s

lived or long-lasting, depending on 

of antigen, the amount of antigen, 

route by which it enters the body. 

24

Natural Natura

Acquired Acquired

SERUM

Immunity can also be influenced by 

inherited genes. When faced with th

antigen, some individuals will resp

forcefully, others feebly, and some n

An immune response can be sparke

only by infection but also by immu

with vaccines. Vaccines contain 

microorganisms—or parts of 

microorganisms—that have been trea

they can provoke an immune respon

not full-blown disease. 

Immunity can also be transferred fr

individual to another by injections 

serum rich in antibodies against a 

particular microbe (antiserum). 
where hepatitis A is widespread. Su

passive immunity typically lasts onl

weeks or months.


Infants are born with weak immune

responses but are protected for the 

months of life by antibodies receive

their mothers before birth. Babies w

nursed can also receive some antib

from breast milk that help to protec

digestive tracts.


Immune Tolerance


Immune tolerance is the tendency o

B lymphocytes to ignore the body’s 

tissues. Maintaining tolerance is im

because it prevents the immune sys

from attacking its fellow cells. Scien

are hard at work trying to understa

the immune system knows when to

respond and when to ignore.


Tolerance occurs in at least two wa

Central tolerance occurs during lym

development. Very early in each im

cell’s life, it is exposed to many of t

molecules in the body. If it encount

these molecules before it has fully


matured, the encounter activates an

internal self-destruct pathway and t

immune cell dies. This process, call

26

and attack healthy tissues. 

Because maturing lymphocytes do n

encounter every molecule in the bo

must also learn to ignore mature ce

tissues. In peripheral tolerance, circ

lymphocytes might recognize a self 

molecule but cannot respond becau

of the chemical signals required to 

the T or B cell are absent. So-called 

anergy, therefore, keeps potentially 

lymphocytes switched off. Peripher

tolerance may also be imposed by a 

class of regulatory T cells that inhib

helper or cytotoxic T-cell activation 

self antigens. 

Vaccines 

Medical workers have long helped t

body’s immune system prepare for 

attacks through vaccination. Vaccin

consist of killed or modified microb

components of microbes, or microb

that trick the body into thinking an 

infection has occurred. An immuniz

person’s immune system attacks th

harmless vaccine and prepares for 

subsequent invasions. Vaccines rem

of the best ways to prevent infectio

diseases and have an excellent safe

record. Previously devastating disea

such as smallpox, polio, and whoop
vaccination programs. 

Disorders of the Immune System 

Allergic Diseases 

The most common types of allergic 

diseases occur when the immune sy

responds to a false alarm. In an alle

person, a normally harmless materi

as grass pollen or house dust is mis

for a threat and attacked. 

Allergies such as pollen allergy are 

to the antibody known as IgE. Like 

antibodies, each IgE antibody is spe

one acts against oak pollen, anothe

against ragweed. 

Autoimmune Diseases 

Sometimes the immune system’s 

recognition apparatus breaks down

the body begins to manufacture T c

antibodies directed against its own 

and organs. Misguided T cells and 

autoantibodies, as they are known, 

contribute to many diseases. For in

T cells that attack pancreas cells co

to diabetes, while an autoantibody 

as rheumatoid factor is common in 

with rheumatoid arthritis. People w

systemic lupus erythematosus (SLE

28

Plasma 

cell 

Mast 

cell 

Chemicals 

Symptoms 

pp

such as ragweed, 

he or she makes large am

of ragweed IgE antibody. 

These IgE molecules attac

themselves to mast cells. 

The second time that pers

has a brush with ragweed

the IgE-primed mast cell w

release its powerful chemi

and the person will suffer t

wheezing and/or sneezing

runny nose, watery eyes, a

itching of allergy. 

IgE 

B cell 
Mature T cell 

Beta cell 

Misguided T cells can attack insulin-producing 

the pancreas, contributing to diabetes. 

antibodies to many types of their o

and cell components. 

No one knows exactly what causes 

autoimmune disease, but multiple f

are likely to be involved. These inc

elements in the environment, such 

viruses, certain drugs, and sunlight

which may damage or alter normal 

cells. Hormones are suspected of pl

role, since most autoimmune diseas

far more common in women than i

Heredity, too, seems to be importan

Many people with autoimmune dise

have characteristic types of self 

marker molecules. 

30

interlocking antigens and antibodie

Normally, immune complexes are r

removed from the bloodstream. Som

however, they continue to circulate

eventually become trapped in the ti

the kidneys, the lungs, skin, joints, 

blood vessels. There they set off re

with complement that lead to inflam

and tissue damage. 

Immune complexes work their misc

many diseases. These include mala

viral hepatitis, as well as many 

autoimmune diseases. 

Small complex 

Endothelial cell 

Glomerular basement 

membrane of kidney 

Large 

complex 

Antigen-antibody complexes can become trap

and damage, the kidneys and other organs. 
or more of its components, the resu

immunodeficiency disorder. 

Immunodeficiency disorders can be 

inherited, acquired through infectio

produced unintentionally by drugs 

those used to treat people with can

those who have received transplant

Temporary immune deficiencies can 

develop in the wake of common vir

infections, including influenza, infe

mononucleosis, and measles. Immu

responses can also be depressed by 

transfusions, surgery, malnutrition, 

smoking, and stress. 

Some children are born with poorly 

functioning immune systems. Some 

flaws in the B cell system and cann

produce antibodies. Others, whose 

is either missing or small and abno

lack T cells. Very rarely, infants are 

lacking all of the major immune de

This condition is known as severe c

immunodeficiency disease or SCID. 

AIDS is an immunodeficiency disor

caused by a virus (HIV) that infects 

immune cells. HIV can destroy or d

vital T cells, paving the way for a v

of immunologic shortcomings. HIV 

can hide out for long periods in im

32 
Cell DNA 

New 

virus 

New AID

virus bud

from T ce

The AIDS virus takes over the machinery of the 

infects, using it to make new viruses. 

cells. As the immune defenses falte

person with AIDS falls prey to unus

often life-threatening infections and 

rare cancers. 

A contagious disease, AIDS is sprea

intimate sexual contact, transfer of 

virus from mother to infant during 

pregnancy, or direct blood contamin

There is no cure for AIDS, but new

developed antiviral drugs can slow 

advance of the disease, at least for 

Researchers also are testing HIV va

in clinical studies. 
cells, can grow uncontrollably, resu

cancer. Leukemias are caused by th

proliferation of white blood cells, o

leukocytes. The uncontrolled growth 

antibody-producing plasma cells ca

to multiple myeloma. Cancers of th

lymphoid organs, known as lympho

include Hodgkin’s disease. 

Immunology and Transplants 

ach year thousands of American 

prolonged by transplanted organs

kidney, heart, lung, liver, and pancr

a transplant to “take,” however, the 

natural tendency to rid itself of fore

tissue must be overridden. 

E

One way, tissue typing, makes sure 

of self on the donor’s tissue are as 

as possible to those of the recipient

cell has a double set of 6 major tiss

antigens, and each of the antigens e

in different individuals, in as many 

varieties. The chance of 2 people ha

identical transplant antigens is abou

1 in 100,000. 

34

powerful immunosuppressive drugs 

as cyclosporine A, or by using labo

manufactured antibodies that attack 

mature T cells. 

Bone Marrow Transplants 

When the immune response is seve

depressed—in infants born with im

disorders or in people with cancer—

possible remedy is a transfer of hea

bone marrow. Introduced into the 

circulation, transplanted bone marr

can develop into functioning B and 

In bone marrow transplants, a clos

is extremely important. Not only is 

danger that the body will reject the 

transplanted bone marrow cells, bu

mature T cells from the bone marro

transplant may counterattack and d

the recipient’s tissues. To prevent th

situation, known as graft-versus-hos

disease, scientists use drugs or anti

to “cleanse” the donor marrow of 

potentially dangerous mature T cell
Cytotoxic 

T cell 

Cancer cell 

Killer cell 

Macropha

A cancer cell can rouse several types of immu

defenses. 

Immunity and Cancer 

hen normal cells turn into can

cells, some of the antigens on 

surface may change. If the immune 

notices the foreign antigens, it laun

body’s defenders, including killer T 

NK cells, and macrophages. But the 

immune system cannot patrol every

to provide bodywide surveillance, f

out and eliminating all cells that be

cancerous. Tumors develop when th

system breaks down or is overwhelm

W

36

weapons. They are using substance

as biological response modifiers, inc

lymphocytes and lymphokines, to b

the patient’s immune responses. In 

cases, biological response modifiers 

injected directly into the patient. Th

also be used in the laboratory to tra

some of the patient’s own lymphoc

into tumor-hungry cells, which are 

injected back into the patient so th

attack the cancer cells. 

Antibodies specially made to recogn

specific cancers can be coupled wit

toxins, or radioactive materials, the

off like “magic bullets” to deliver th

lethal cargo directly to the target ca

Antibody Toxin

Cancer cell 

destroyed 

Cancer 

cell 

N

ce

Tumor 

antigen 

Antibodies targeted against cancer cells can b

with toxins, drugs, or radioactive substances, w

can deliver directly to the cancer cell. 
with receptors for the lymphokine. 

Radioactively labeled antibodies ca

be used to track down hidden nests 

cancer cells (metastases). 

Still other researchers are testing 

therapeutic cancer vaccines. These 

from traditional vaccines, which ar

before disease onset to protect a pe

from future infections. Cancer vacc

used after the cancer has arisen, an

designed to help the immune system 

off the illness. 

The immune system often responds 

or not at all to cancer cells. Cancer 

vaccines try to improve on the natu

anticancer response by stimulating 

killer T-cell responses against a tum

Although such vaccines are general

able to destroy a tumor if given as 

form of treatment, research suggest

can be effective partners if adminis

along with other forms of treatmen

38

E

vidence is mounting that the imm

system and the nervous system a

linked in several ways. One well-kn

connection involves the adrenal gla

response to stress messages from th

the adrenal glands release hormone

the blood. In addition to helping a 

respond to emergencies by mobilizi

body’s energy reserves, these “stres

hormones” can stifle the protective 

of antibodies and lymphocytes. 

Hormones and other chemicals kno

convey messages among nerve cell

been found to “speak” to cells of th

immune system. Indeed, some imm

cells are able to manufacture typica

cell products, while some lymphok

transmit information to the nervous 

system. What’s more, the brain ma

messages directly down nerve cells 

immune system. Networks of nerve 

have been found connecting to the 

lymphoid organs. 
Scientists are now able to mass-p

immune cell secretions, both ant

and lymphokines, as well as specia

immune cells. The ready supply of 

materials not only has revolutioniz

study of the immune system itself b

has had an enormous impact on m

agriculture, and industry. 

Monoclonal antibodies are identical 

antibodies made by the many desce

(clones) of a single B cell. Because 

unique specificity for different mole

monoclonal antibodies are promisin

treatments for a range of diseases. 

Researchers make monoclonal antib

by injecting a mouse with a target 

and then fusing B cells from the mo

with another long-lived cell. The re

hybrid cell becomes a type of antib

factory, turning out identical copies 

antibody molecules specific for the 

target antigen. 

Mouse antibodies are “foreign” to p

however, and might trigger their ow

immune response when injected in

human. Therefore, researchers have 

to study “humanized” monoclonal 

antibodies. To construct these mole

scientists take the antigen-binding p

of a mouse antibody and attach it t

40

Antibody-producing 

plasma cell 

Monoclonal antibodies 

Long-liv

plasma 

Cells fuse into 

a hybridoma 

Antigen 

Monoclonal antibody technology makes it pos

mass produce specific antibodies to order. 

human antibody scaffolding, greatly 

reducing the foreign portion of the m

Because they recognize very specifi

molecules, monoclonal antibodies a

in diagnostic tests to identify invad

pathogens or changes in the body’s 

proteins. In medicine, monoclonal 

antibodies can attach to cancer cell
other cases, monoclonal antibodies 

carry potent toxins into select cells

killing the cell while leaving its 

neighbors untouched. 

Genetic Engineering 

Genetic engineering allows scientis

pluck genes—segments of the here

material, DNA—from one type of o

and combine them with genes of a 

organism. In this way relatively sim

organisms such as bacteria or yeas

induced to make quantities of hum

proteins, including hormones such 

insulin as well as lymphokines and 

monokines. They can also manufac

proteins from infectious agents, suc

the hepatitis virus or HIV, for use in v

Gene Therapy 

Genetic engineering also holds prom

gene therapy—replacing altered or 

genes or adding helpful genes. Sev

combined immunodeficiency diseas

prime candidate for gene therapy. S

caused by the lack of an enzyme du

single missing gene. A genetically 

engineered version of the missing g

be introduced into cells taken from 

patient’s bone marrow. After treate

marrow cells begin to produce the 

they can be injected back into the 

42

Strand of DNA 

from cytokineproducing cell 

Plasmid—

of DNA—f

bacterium 

Plasmid is 

open 

Cytokine gene 

is cut out of 

DNA 

Hybrid plasmid 

is put back into 

bacterium 

Bacterium makes 

human cytokines 

Cytokine gene 

is spliced into 

plasmid 

Genetic engineering transforms simple organisms into factories for makin

human proteins. 
removing cancer-fighting lymphocy

the cancer patient’s tumor, insertin

that boosts the lymphocytes’ ability 

make quantities of a natural antica

product, then growing the restructu

cells in quantity in the laboratory. 

These cells are injected back into th

patient, where they can seek out th

tumor and deliver large doses of th

anticancer chemical. 

Immunoregulation 

Research into the delicate checks a

balances that control the immune r

is increasing knowledge of normal 

abnormal immune functions. Some

may be possible to treat diseases su

systemic lupus erythematosus by 

suppressing parts of the immune sy

that are overactive. 

By transplanting immature human 

tissues or immune cells into SCID m

scientists have created a living mod

the human immune system. This an

model promises to be immensely va

helping scientists understand the im

system and manipulate it benefit 

human health. 

44

immune 

Immature tissue

human 

immune 

cells 

Mouse kid

Immuno-incompetent SCID-hu mouse 

The SCID-hu mouse provides a means of studying th

immune system in action. 

Summary 

lthough scientists have learned 

about the immune system, they 

continue to study how the body lau

attacks that destroy invading micro

infected cells, and tumors while ign

healthy tissues. New technologies f

identifying individual immune cells 

now letting scientists quickly determ

which targets are triggering an imm

response. Improvements in microsc

are permitting the first-ever observa

of B cells, T cells, and other cells a

interact within lymph nodes and ot

body tissues. 

A

In addition, scientists are rapidly 

unraveling the genetic blueprints th

direct the human immune response 
combination of new technology and 

expanded genetic information will n

doubt teach us even more about ho

body protects itself from disease. 

46

syndrome)—life-threatening disease 

caused by the human immunodefic

virus, which breaks down the body

immune defenses. 

adenoids—see tonsils. 

adrenal gland—a gland located on 

kidney that secretes hormones regu

metabolism, sexual function, water 

balance, and stress. 

allergen—any substance that cause

an allergy. 

allergy—a harmful response of the 

system to normally harmless substa

antibodies—molecules (also called 

immunoglobulins) produced by a B 

response to an antigen. When an a

attaches to an antigen, it helps the 

destroy or inactivate the antigen. 

antigen—a substance or molecule t

recognized by the immune system. 

molecule can be from foreign mate

as bacteria or viruses. 

antiserum—a serum rich in antibod

against a particular microbe. 

appendix—lymphoid organ in the i
autoimmune disease—disease that 

when the immune system mistaken

attacks the body’s own tissues. Exa

include multiple sclerosis, type I di

rheumatoid arthritis, and systemic 

lupus erythematosus. 

B cells—small white blood cells cru

to the immune defenses. Also know 

B lymphocytes, they come from bon

marrow and develop into blood cel

called plasma cells, which are the s

of antibodies. 

bacteria—microscopic organisms co

of a single cell. Some cause disease

basophils—white blood cells that 

contribute to inflammatory reaction

Along with mast cells, basophils ar

responsible for the symptoms of all

biological response modifiers—subs

either natural or synthesized, that b

direct, or restore normal immune 

defenses. They include interferons, 

interleukins, thymus hormones, an

monoclonal antibodies. 

blood vessels—arteries, veins, and 

capillaries that carry blood to and f

the heart and body tissues. 

48

source of all blood cells. 

chemokines—certain proteins that s

both specific and general immune c

and help coordinate immune respo

and inflammation. 

clone—a group of genetically identi

or organisms descended from a sin

common ancestor; or, to reproduce 

identical copies. 

complement—a complex series of b

proteins whose action “complemen

work of antibodies. Complement de

bacteria, produces inflammation, an

regulates immune reactions. 

complement cascade—a precise seq

events, usually triggered by antigen

antibody complexes, in which each 

component of the complement syst

activated in turn. 

cytokines—powerful chemical subst

secreted by cells that enable the bo

cells to communicate with one ano

Cytokines include lymphokines pro

by lymphocytes and monokines pro

by monocytes and macrophages. 
marker and can destroy body cells 

infected by viruses or transformed 

by cancer. 

DNA (deoxyribonucleic acid)—a lon

molecule found in the cell nucleus; 

carries the cell’s genetic informatio

enzyme—a protein produced by 

living cells that promotes the 

chemical processes of life without 

itself being altered. 

eosinophils—white blood cells that 

contain granules filled with chemic

damaging to parasites, and enzyme

that affect inflammatory reactions. 

epithelial cells—cells making up the 

epithelium, the covering for interna

and external body surfaces. 

fungi—members of a class of relati

primitive vegetable organisms. The

include mushrooms, yeasts, rusts, 

molds, and smuts. 

genes—units of genetic material (D

inherited from a parent. Genes carr

the directions a cell uses to perform 

specific function. 

graft rejection—an immune respons

against transplanted tissue. 

50

cells attack the tissues of the recipi

granules—membrane-bound organe

within cells where proteins are stor

before secretion. 

granulocytes—phagocytic white blo

filled with granules organisms. 

Neutrophils, eosinophils, basophils

mast cells are examples of granuloc

growth factors—chemicals secreted 

that stimulate proliferation of or ch

in the physical properties of other c

helper T cells (Th cells)—a subset o

that carry the CD4 surface marker 

essential for turning on antibody pro

activating cytotoxic T cells, and ini

many other immune functions. 

HIV (human immunodeficiency viru

virus that causes AIDS. 

immune response—reaction of the i

system to foreign substances. 

immunoglobulins—a family of large 

protein molecules, also known as 

antibodies, produced by B cells. 

immunosuppressive—capable of red

immune responses. 
infection, as the result of increased 

flow and an influx of immune cells 

and secretions. 

interferons—proteins produced by c

stimulate anti-virus immune respon

alter the physical properties of immu

interleukins—a major group of 

lymphokines and monokines. 

leukocytes—all white blood cells. 

lymph—a transparent, slightly yello

fluid that carries lymphocytes, bath

the body tissues, and drains into th

lymphatic vessels. 

lymph nodes—small bean-shaped o

of the immune system, distributed 

throughout the body and linked by 

lymphatic vessels. Lymph nodes ar

garrisons of B, T, and other immun

lymphatic vessels—a bodywide netw

of channels, similar to the blood ve

which transport lymph to the immu

organs and into the bloodstream. 

lymphocytes—small white blood ce

produced in the lymphoid organs a

paramount in the immune defenses

B cells and T cells are lymphocytes

52

develop and congregate. They inclu

the bone marrow, thymus, lymph n

spleen, and various other clusters o

lymphoid tissue. Blood vessels and 

lymphatic vessels are also lymphoid 

lymphokines—powerful chemical 

substances secreted by lymphocyte

These molecules help direct and re

the immune responses. 

macrophage—a large and versatile 

cell that devours invading pathogen

other intruders. Macrophages stimu

other immune cells by presenting t

with small pieces of the invaders. 

major histocompatibility complex (M

group of genes that controls severa

of the immune response. MHC gene

for “self” markers on all body cells

mast cell—a granulocyte found in t

The contents of mast cells, along w

those of basophils, are responsible 

symptoms of allergy. 

memory cells—a subset of T cells a

cells that have been exposed to ant

and can then respond more readily 

the immune system encounters tho

antigens again. 
and protozoa. 

microorganisms—microscopic organ

including bacteria, virus, fungi, pla

and parasites. 

molecule—the smallest amount of a 

specific chemical substance. Large 

molecules such as proteins, fats, 

carbohydrates, and nucleic acids ar

building blocks of a cell, and a gen

determines how each molecule is p

monoclonal antibodies—antibodies 

produced by a single cell or its iden

progeny, specific for a given antige

tools for binding to specific protein 

molecules, they are invaluable in re

medicine, and industry. 

monocytes—large phagocytic white 

cells which, when entering tissue, d

into macrophages. 

monokines—powerful chemical sub

secreted by monocytes and macrop

These molecules help direct and re

the immune responses. 

54

and kill cells lacking self antigens. 

target recognition molecules are dif

from T cells. 

neutrophil—white blood cell that is 

abundant and important phagocyte

organisms—individual living things

parasites—plants or animals that li

grow, and feed on or within anothe

living organism. 

passive immunity—immunity resul

from the transfer of antibodies or 

antiserum produced by another ind

pathogen—a disease-causing organ

phagocytes—large white blood cells 

contribute to the immune defenses 

ingesting microbes or other cells an

foreign particles. 

phagocytosis—process by which on

engulfs another cell or large particl

plasma cells—large antibody-produ

cells that develop from B cells. 

platelet—cellular fragment critical f

blood clotting and sealing off woun
fluid contains the antibodies that w

present in the whole blood. 

spleen—a lymphoid organ in the 

abdominal cavity that is an importa

center for immune system activities

stem cells—immature cells from wh

cells derive. The bone marrow is ri

stem cells, which become specializ

blood cells. 

T cells—small white blood cells (al

known as T lymphocytes) that reco

antigen fragments bound to cell sur

by specialized antibody-like recepto

“T” stands for thymus, where T cel

acquire their receptors. 

T lymphocytes—see T cells. 

thymus—a primary lymphoid organ

in the chest, where T lymphocytes 

proliferate and mature. 

tissue typing—see histocompatibility 

tissues—groups of similar cells join

perform the same function. 

tolerance—a state of immune 

nonresponsiveness to a particular a

or group of antigens. 

56

of the throat. 

toxins—agents produced in plants a

bacteria, normally very damaging t

vaccines—preparations that stimula

immune response that can prevent 

infection or create resistance to an 

infection. They do not cause diseas

viruses—microorganisms composed 

piece of genetic material—RNA or D

surrounded by a protein coat. Virus

reproduce only in living cells. 
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